April 11th

Researchers at the Hebrew University of Jerusalem have discovered a previously unknown mechanism whereby tumor cells invade normal tissues, spreading cancer through various organs. The ability of tumor cells to invade adjacent structures is a prerequisite for metastasis and distinguishes malignant tumors from benign ones. Thus, understanding the mechanisms that drive malignant cells to invade and a possible avenue for halting that mechanism could have tremendous potential for enhancing early detection of malignant cells and for therapeutic treatment.It has previously been assumed that tumor cells turn invasive upon accumulation of multiple mutations, each giving the cancer cell some invasive properties. Now, Professor Yinon Ben-Neriah and Dr. Eli Pikarsky of the Institute for Medical Research Israel-Canada at the Hebrew University Faculty of Medicine and their colleagues are reporting an alternative mechanism through which tumor cells become invasive. They found a program that is operated by a concerted group of genes that, when activated together, confer invasive properties upon epithelial cells. (Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands.) An article reporting their work appeared in the February 17, 2011 issue of the journal Nature. Interestingly, the expression of this entire gene group is normally suppressed by a single gene – p53 – that is considered as the most important tumor suppressor but unfortunately is inactivated in the majority of human cancers. Some key properties of the protein produced by the p53 gene -- arresting cell growth and induction of cell death – were previously discovered by Dr. Moshe Oren of the Weizmann Institute of Science, another member of the current research team.

A diet high in saturated fat is a key contributor to type 2 diabetes, a major health threat worldwide. Several decades ago scientists noticed that people with type 2 diabetes have overly active immune responses, leaving their bodies rife with inflammatory chemicals. In addition, people who acquire the disease are typically obese and are resistant to insulin, the hormone that removes sugar from the blood and stores it as energy. For years no one has known exactly how the three characteristics are related. But a handful of studies suggest that they are inextricably linked. New research from the University of North Carolina at Chapel Hill School of Medicine adds clarity to the connection. The study published online April 10, 2011, in the journal Nature Immunology finds that saturated fatty acids, but not the unsaturated type can activate immune cells to produce an inflammatory protein, called interleukin-1beta.“The cellular path that mediates fatty acid metabolism is also the one that causes interleukin-1beta production,” says senior study co-author Dr. Jenny Y. Ting, William Kenan Rand Professor in the Department of Microbiology and Immunology. “Interleukin-1beta then acts on tissues and organs such as the liver, muscle and fat (adipose) to turn off their response to insulin, making them insulin-resistant. As a result, activation of this pathway by fatty acid can lead to insulin resistance and type 2 diabetes symptoms.” Dr. Ting is also a member of the UNC Lineberger Comprehensive Cancer Center, and the UNC Inflammatory Diseases Institute. [Press release] [Nature Immunology abstract]

Using sinus tissue removed during surgery at University of Wisconsin Hospital and Clinics, researchers at the University of Wisconsin-Madison have managed to grow a recently discovered species of human rhinovirus (HRV), the most frequent cause of the common cold, in culture. The researchers found that the virus, which is associated with up to half of all HRV infections in children, has reproductive properties that differ from those of other members of the HRV family. The accomplishments, reported in Nature Medicine on April 10, 2011, should allow antiviral compounds to be screened to see if they stop the virus from growing. The report sheds light on HRV-C, a new member of the HRV family that also includes the well-known HRV-A and HRV-B. Discovered five years ago, HRV-C has been notoriously difficult to grow in standard cell cultures and, therefore, impossible to study. "We now have evidence that there may be new approaches to treating or preventing HRV-C infections," says senior author Dr. James Gern, professor of medicine at the UW-Madison School of Medicine and Public Health and an asthma expert at American Family Children's Hospital. Future drugs could be especially useful for children and adults who have asthma and other lung problems, Dr. Gern says. Recent studies have shown that in addition to its major role in the common cold, HRV-C is responsible for between 50 percent and 80 percent of asthma attacks. HRV-C is a frequent cause of wheezing illnesses in infants and may be especially likely to cause asthma attacks in children. HRV infections of all kinds also can greatly worsen chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Like other scientists, Dr. Yury Bochkov, a virologist in Gern's lab, was unable to grow HRV-C in standard cell lines.

April 10th

When viruses attack, one molecule (interferon) more than any other fights back. Interferon triggers the activation of more than 350 genes, and despite the obvious connection, the vast majority have never been tested for antiviral properties. A team of researchers, led by scientists from Rockefeller University, for the first time has carried out a comprehensive, systematic evaluation of the antiviral activity of interferon-induced factors. The findings, published online on April 10, 2011, in the journal Nature, are a first step toward unraveling how these naturally occurring molecules work to inhibit viruses. "We hope this study will open the door to future work on the mechanisms of antiviral molecules," says first author Dr. John Schoggins, a postdoctoral associate in Dr. Charles M. Rice's Laboratory of Virology and Infectious Disease at Rockefeller. "Such mechanistic studies may set the stage for the development of new and much-needed drugs to combat a diverse array of viruses that pose significant health threats to people worldwide." The researchers were interested in type I interferon, a cellular molecule that is made when a person becomes infected with certain viruses. Type I interferon is used clinically in the treatment of some viral diseases, such as hepatitis C, and its presence has been shown to significantly limit the severity of certain viral infections. Dr. Schoggins and his colleagues, including researchers from the Aaron Diamond AIDS Research Center and the Howard Hughes Medical Institute, systematically evaluated the majority of common interferon-induced genes, one by one, to determine which of them had antiviral activity against a panel of disease-causing viruses, including the hepatitis C virus, HIV, West Nile virus, the yellow fever virus, and chikungunya virus.

April 8th

A single change to even one of the thousands of DNA codes that make up each gene in the human genome can result in severe diseases such as cancer, cystic fibrosis, or muscular dystrophy. A similarly minor change in the DNA of a virus or bacteria can give rise to drug-resistant strains that are difficult for physicians to treat with standard drug therapies. For these reasons, scientists have long sought ways to study the effects genetic mutations can have on an organism but have been hampered in these efforts by an inability to easily and efficiently produce and analyze the thousands of potential changes possible in even one small gene. A new study by scientists at the University of Massachusetts Medical School, published in PNAS online on April 4, 2011, describes a novel technique to produce all potential individual mutations and using deep sequencing technology simultaneously analyze each change's impact on the cell. "In nature, genetic mutations actually occur infrequently and at random," said Dr. Daniel N. A. Bolon, assistant professor of biochemistry & molecular pharmacology and lead author of the PNAS study. "But these small changes have profound consequences on an organism's ability to survive. We've developed an approach that allows us to generate all the possible individual changes and, at the same time in the same test tube, study the impact of each change." Using sequencing technology inspired by the human genome project, Bolon and colleagues have developed a method called EMPIRIC to analyze hundreds of different mutations in a single test tube. Ordinarily used to read a DNA sequence over an entire genome, Dr. Bolon utilizes the ability of a band-aid-sized sequencing chip to accurately count and record the abundance of hundreds of distinct cells in a test tube that differ by individual mutations.

A growing body of research suggests that caffeine disrupts glucose metabolism and may contribute to the development and poor control of type 2 diabetes, a major public health problem. A review article in the March 2011 inaugural issue of Journal of Caffeine Research: The International Multidisciplinary Journal of Caffeine Science, a quarterly peer-reviewed journal from Mary Ann Liebert, Inc. publishers, examines the latest evidence, contradicting earlier studies suggesting a protective effect of caffeine. The entire issue is available free online. Dr. James Lane, of Duke University, describes numerous studies that have demonstrated caffeine's potential for increasing insulin resistance (impaired glucose tolerance) in adults that do not have diabetes, an effect that could make susceptible individuals more likely to develop the disease. In adults with type 2 diabetes, studies have shown that the increase in blood glucose levels that occurs after they eat carbohydrates is exaggerated if they also consume a caffeinated beverage such as coffee. This effect could contribute to higher glucose levels in people with diabetes and could compromise treatment aimed at controlling their blood glucose. "More than 220 million people worldwide have diabetes, says Editor-in-Chief Dr. Jack E. James, School of Psychology, National University of Ireland, Galway, Ireland. "The links that have been revealed between diabetes and the consumption of caffeine beverages (especially coffee) are of monumental importance when it is acknowledged that more than 80% of the world's population consumes caffeine daily. Dr.

Researchers from the CHUM Research Centre (CRCHUM) in Montreal, Canada, and colleagues have identified a gene that, when mutated, predisposes people to both autism and epilepsy. Led by the neurologist Dr. Patrick Cossette, the research team found a severe mutation of the synapsin gene (SYN1) in all members of a large French-Canadian family suffering from epilepsy, including individuals also suffering from autism. This study also includes an analysis of two cohorts of individuals from Quebec, which made it possible to identify other mutations in the SYN1 gene among 1% and 3.5% of those suffering respectively from autism and epilepsy, while several carriers of the SYN1 mutation displayed symptoms of both disorders. "The results show for the first time the role of the SYN1 gene in autism, in addition to epilepsy, and strengthen the hypothesis that a deregulation of the function of synapse because of this mutation is the cause of both diseases," notes Dr. Cossette, who is also a professor with the Faculty of Medicine at the Université de Montréal. He adds that "until now, no other genetic study of humans has made this demonstration." The different forms of autism are often genetic in origin and nearly a third of people with autism also suffer from epilepsy. The reason for this comorbidity is unknown. The synapsin gene plays a crucial role in the development of the membrane surrounding neurotransmitters, also referred to as synaptic vesicles. These neurotransmitters ensure communication between neurons. Although mutations in other genes involved in the development of synapses (the functional junction between two neurons) have previously been identified, this mechanism has never been proved in epilepsy in humans until the present study.

April 7th

Components in soybeans increase radiation's ability to kill lung cancer cells, according to a Wayne State University study published in the April 2011 issue of the Journal of Thoracic Oncology, the official monthly journal of the International Association for the Study of Lung Cancer. "To improve radiotherapy for lung cancer, we are studying the potential of natural non-toxic components of soybeans, called soy isoflavones, to augment the effect of radiation against the tumor cells and at the same time protect normal lung cells against radiation injury," said Dr. Gilda Hillman, associate professor in the Department of Radiation Oncology at Wayne State University's School of Medicine and the Karmanos Cancer Institute, who led the team of researchers. "These natural soy isoflavones can sensitize cancer cells to the effects of radiotherapy by inhibiting the survival mechanisms that cancer cells activate to protect themselves," Dr. Hillman said. "At the same time, soy isoflavones can also act as antioxidants, which protect normal tissues against unintended damage from the radiotherapy." Dr. Hillman and her team demonstrated that soy isoflavones increase killing of cancer cells by radiation via blocking DNA repair mechanisms, which are turned on by the cancer cells to survive the damage caused by radiation. Human A549 non-small cell lung cancer (NSCLC) cells that were treated with soy isoflavones before radiation showed more DNA damage and less repair activity than cells that received only radiation. Researchers used a formulation consisting of the three main isoflavones found in soybeans, including genistein, daidzein and glycitein.

For many types of cancer, the original tumor itself is usually not deadly. Instead, it's the spread of a tiny subpopulation of cells from the primary tumor to other parts of the body—the process known as metastasis—that all too often kills the patient. Now, researchers at Albert Einstein College of Medicine of Yeshiva University have identified two molecules that enable cancer to spread inside the body. These findings could eventually lead to therapies that prevent metastasis by inactivating the molecules. The regulatory molecules are involved in forming invadopodia, the protrusions that enable tumor cells to turn metastatic – by becoming motile, degrading extracellular material, penetrating blood vessels and, ultimately, seeding themselves in other parts of the body. The research appears online on April 7, 2011 in Current Biology. The study's senior author is Dr. John Condeelis, co-chair and professor of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center and holder of the Judith and Burton P. Resnick Chair in Translational Research at Einstein. Dr. Condeelis and his team identified two molecules (p190RhoGEF and p190RhoGAP) that regulate the activity of RhoC, an enzyme that plays a crucial role during tumor metastasis and that has been identified as a biomarker for invasive breast cancer. "In vitro as well as in vivo studies have shown that RhoC's activity is positively correlated with increased invasion and motility of tumor cells," said corresponding author Dr. Jose Javier Bravo-Cordero, Ph.D., a postdoctoral fellow in the labs of Dr. Condeelis and assistant professor Louis Hodgson, Ph.D., in the Gruss Lipper Biophotonics Center and the department of anatomy and structural biology.

A phase 2 clinical trial for the treatment of a severe form of age-related macular degeneration (AMD) called geographic atrophy (GA) has become the first study to show the benefit of a therapy to slow the progression of vision loss for this disease. The results highlight the benefit of the use of a neurotrophic factor to treat GA and provide hope to nearly one million Americans suffering from GA. The multi-center research team, including Dr. Kang Zhang, of the University of California, San Diego, Shiley Eye Center, the lead author of the paper and one of the leading investigators in the study, found that long-term delivery of ciliary neurotrophic factor (CNTF) served to re-nourish the retina and stop or slow the loss of visual acuity caused by the disorder. The results were published online on March 28, 2011, in PNAS. According to Dr. Zhang -- professor of ophthalmology and human genetics at the UCSD School of Medicine and director of UCSD's Institute of Genomic Medicine – there is currently no effective treatment for dry AMD or GA, though there is a very big need. "This could open the door to long-term treatment of dry AMD, using a simple surgical procedure." AMD is a leading cause of vision loss in Americans age 60 and older. It is a disease that causes cells in the macula – the part of the eye that allows us to see in fine detail – to die. There are two forms of the disorder, wet and dry AMD. GA is considered the end stage of dry AMD, where central vision is lost. According to the National Eye Institute, wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid. The blood and fluid raise the macula from its normal place at the back of the eye, resulting in rapid loss of central version.